Long-term studies of socially stressed mice living in male-female colonies in Henry-Stephens complex population cages have established the development of fixed high blood pressure, progressive arteriosclerosis, and myocardial fibrosis, together with chronic interstitial nephritis and elevated plasma renin. These pathophysiological consequences of chronic neuroendocrine arousal in competing mice develop over a period of 6 months. In the 2 1/2 year lifespan of the mouse this is equivalent to 15 years in man. Our project will determine whether standard antihypertensive treatment, i.e., a low-salt diet or a beta blocker (Metoprolol), with or without a vasodilator (Apresoline) will control stress-induced pathology. Measurements will include behavior (breeding and fighting, as indicated by scarring), monthly blood pressure, pulse rate, and body weight; and at termination, plasma renin, and corticosterone or testosterone or both; adrenal catecholamines or tyrosine hydroxylase or both, together with tissue weights (heart, kidneys, adrenals, testes, seminal vesicles); and heart and kidney tissue pathology. Sodium balance and the level of drugs in plasma will be measured. Preliminary observations indicate that a modified special low-salt Purina lab chow, which provides the equivalent of 10 g/70 kg body weight in man, will reduce the blood pressure of a socially stressed mouse colony to near normal; however renal pathology persists. Metoprolol also successfully reduces systolic pressure to normal but has not prevented the gradual development of renal failure in repeated studies. Although blood pressure remains normal in these stressed colonies, pathophysiological changes are not prevented by a limited antihypertensive regime. Our goal is to determine the mechanisms underlying the continuing pathophysiology and the antihypertensive regime, if any, that will prevent deterioration; in particular, whether the addition of Apresoline to the beta blocker will maintain pathology-free mice in population cages. Another goal is to determine the optimum level of salt, which controls blood pressure, without disturbing healthy competitive behavior.